X-124334064-A-T

Position:

• chrX-124334064-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001355534.2(TEX13D):​c.1147A>T​(p.Met383Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 933,998 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 132 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., 11 hem., cov: 21)
  • Exomes 𝑓: 0.00050 (0 hom. 121 hem.)
• Consequence: TEX13D NM_001355534.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.687

Genes affected

TEX13D (HGNC:52278): (TEX13 family member D) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

SH2D1A (HGNC:10820): (SH2 domain containing 1A) This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062076658).
• BP6: Variant X-124334064-A-T is Benign according to our data. Variant chrX-124334064-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX13D	NM_001355534.2	c.1147A>T	p.Met383Leu	missense_variant	1/1	ENST00000632372.3	NP_001342463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX13D	ENST00000632372.3	c.1147A>T	p.Met383Leu	missense_variant	1/1		NM_001355534.2	ENSP00000488696	P1

Frequencies

GnomAD3 genomes AF: 0.000330 AC: 36 AN: 109250 Hom.: 0 Cov.: 21 AF XY: 0.000346 AC XY: 11 AN XY: 31810

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000955

Gnomad ASJ AF: 0.00191

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000342

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000517

Gnomad OTH AF: 0.000678

GnomAD4 exome AF: 0.000504 AC: 416 AN: 824702 Hom.: 0 Cov.: 31 AF XY: 0.000475 AC XY: 121 AN XY: 254728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000310

Gnomad4 ASJ exome AF: 0.00197

Gnomad4 EAS exome AF: 0.0000489

Gnomad4 SAS exome AF: 0.0000705

Gnomad4 FIN exome AF: 0.000555

Gnomad4 NFE exome AF: 0.000531

Gnomad4 OTH exome AF: 0.000267

GnomAD4 genome AF: 0.000329 AC: 36 AN: 109296 Hom.: 0 Cov.: 21 AF XY: 0.000345 AC XY: 11 AN XY: 31864

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000954

Gnomad4 ASJ AF: 0.00191

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000342

Gnomad4 NFE AF: 0.000517

Gnomad4 OTH AF: 0.000670

Alfa AF: 0.000918 Hom.: 5

Bravo AF: 0.000389

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

TEX13D: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.55
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.062	T
Sift4G	Benign	0.44	T
Vest4		0.20
GERP RS		-1.4
Varity_R		0.31
gMVP		0.043

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs181190185; hg19: chrX-123467914;